CG2AT2: an Enhanced Fragment-Based Approach for Serial Multi-scale Molecular Dynamics Simulations
Owen N Vickery1, Phillip J Stansfeld1
1School of Life Sciences & Department of Chemistry, University of Warwick, Gibbet Hill Campus, Coventry CV4 7AL, U.K.
Journal of Chemical Theory and Computation
|September 7, 2021
Summary
This study introduces an enhanced protocol to convert coarse-grained molecular dynamics simulations to atomistic resolution. This method accurately refines macromolecular complexes, including membrane proteins, for detailed analysis.
Area of Science:
- Computational biology
- Structural biology
- Biophysics
Background:
- Coarse-grained molecular dynamics (CGMD) enables large-scale simulations of macromolecular complexes.
- A gap exists in efficiently converting CGMD models to high-resolution atomistic detail for analysis.
Purpose of the Study:
- To present an enhanced fragment-based protocol for converting coarse-grained models to atomistic resolution.
- To enable accurate refinement and analysis of macromolecular complexes, particularly integral membrane proteins.
Main Methods:
- Developed an enhanced fragment-based protocol for resolution conversion.
- Applied the protocol to diverse systems including integral membrane proteins in phospholipid bilayers.
- Evaluated simulations based on protein stereochemistry, conformational stability, and lipid-protein interactions.
Main Results:
- The protocol successfully generated accurate and well-equilibrated atomic-level descriptions.
- Demonstrated suitability for integral membrane proteins, membrane-anchored, and soluble complexes.
- Validated the approach across 11 systems of varying complexity.
Conclusions:
- The enhanced protocol provides a robust method for transitioning from coarse-grained to atomistic simulations.
- Facilitates detailed structural and dynamic analysis of complex biological systems.
- Offers a valuable tool for computational structural biology research.
